Core 2: Project Summary/Abstract Over the past 15 years, the primary goal of the MD Anderson SPORE in Melanoma has been to translate our fundamental understanding of melanoma into improved patient care by improving melanoma prevention, detection, and therapy. Building upon this experience and to further this goal, it is essential to continue to conduct high-impact, well-planned, translational research involving well-annotated curated biospecimens and relevant clinical data to identify the pathophysiologic mechanisms of melanoma and the metastatic cascade, identify biomarkers and targets for antitumor therapy, and evaluating the mechanisms of response and resistance in new treatment strategies. The Melanoma Clinical Database, Tissue Resource, and Translational Pathology Core (Core 2) will maintain a comprehensive, prospective, relational database containing detailed clinical, pathologic, and outcome data for patients with melanoma seen and treated at MD Anderson. Core 2 will also procure and process tissue, blood, and cerebrospinal fluid specimens in support of the SPORE Projects, and will facilitate the downstream analysis for histopathologic features, including immunohistochemistry with image analysis and molecular analysis of prospectively collected melanoma specimens as well as archival material. A noteworthy addition for the current SPORE submission is the development and integration of the uveal melanoma database module as well as the addition of an automated request module for sample distribution to facilitate all SPORE-based and other research projects. The current proposal includes expanded efforts and infrastructure to support the optimization of fresh tissue collection and processing of distant metastases from image- guided biopsies, analyte (DNA, RNA, protein) extraction from prospectively collected and archival tissue samples suitable for molecular and immunological interrogation, and the conduct of NanoString gene expression profiling. The samples and/or analytes isolated from biospecimens will be distributed to SPORE projects and other investigators in accordance with our Core operating procedures, and Core 2 will work with each of the SPORE projects, CCSG Cores, collaborator laboratories, and with the Administrative and Biostatistics Cores, to ensure maximum efficiency of tissue/derivatives. Together, Core 2 will be a resource for clinicopathologic data, well-annotated biospecimens, and for optimized acquisition, processing, distribution and analyses that facilitate integration of conventional biomarkers, molecular and immunologic data, with clinicopathologic, treatment, recurrence and follow-up. Overall, these approaches will facilitate the discovery of clinically impactful predictive and prognostic biomarkers, as well as enhanced approaches to anti-tumor therapy across several clinically unmet needs for patients with melanoma. This centralized resource will contribute significantly to the success of the multidisciplinary and translational research projects outlined in this proposal.